The development of effective treatments for cocaine addiction will likely await the identification of neuroadaptations produced by repeated administration of cocaine. Recently, it has been revealed that glutamate neurotransmission in the nucleus accumbens is critical for the expression of behavioral sensitization and reinstatement of cocaine-seeking behavior, two animal models of drug-induced craving and paranoid psychosis. The aim of this proposal is to characterize cocaine-induced neuroadaptations in the release and reuptake of extracellular glutamate. Toward this end, rats will receive repeated administration of saline or cocaine, and in vivo and in vitro techniques will be used to examine cocaine-induced alterations in a) vesicular release of glutamate, b) Na- dependent reuptake of glutamate, and c) cystine/glutamate exchange. The experiments outlined in this proposal will use microdialysis for in vivo measures of glutamate transmission, which is somewhat controversial due to the fact that basal levels of glutamate do not appear to be of vesicular origin. Thus, the proposed experiments will also endeavor to address this controversy by determining the origin of basal levels of extracellular glutamate as estimated by microdialysis.